1.
Changes in apoptosis factors in lens epithelial cells of cataract patients with diabetes mellitus.
Kim, B, Kim, SY, Chung, SK
Journal of cataract and refractive surgery. 2012;(8):1376-81
Abstract
PURPOSE To determine and compare the expression of apoptotic factors Bax and Bcl-2 in lens epithelial cells (LECs) of cataract patients with and without diabetic retinopathy (DR), the duration of diabetes mellitus (DM), and the glycated hemoglobin (HbA1c) level. SETTING St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea. DESIGN Randomized prospective study. METHODS Patients were classified into 3 groups as follows: patients without DM (Group 1), patients with DM but without DR (Group 2), and diabetic patients with DR (Group 3). Data on the duration of DM and the HbA1c levels were recorded. The anterior capsule was obtained from the patients after cataract surgery, and immunohistochemical stains of Bax and Bcl-2 were performed. The stained anterior capsules were analyzed by reactivity scoring. RESULTS Each group comprised 20 eyes. There was a statistically significant increase in Bax expression in all groups (P<.001). The Bcl-2 expression increased more in Group 2 and Group 3 than in Group 1, although the difference was not significant (P=.615). With a longer duration of DM and higher HbA1c level, Bax expression significantly increased but Bcl-2 was weakly expressed. CONCLUSIONS The apoptosis in LECs increased in cataract patients with DM and with or without DR. Using this knowledge on the regulation of apoptosis will permit better identification of the factors involved in the etiology of diabetes and may result in new therapies for diabetic cataract. FINANCIAL DISCLOSURE No author has a financial or proprietary interest in any material or method mentioned.
2.
Sodium orthovanadate affects growth of some human epithelial cancer cells (A549, HTB44, DU145).
Klein, A, Holko, P, Ligeza, J, Kordowiak, AM
Folia biologica. 2008;(3-4):115-21
Abstract
Within the concentration range of 1-20 microM, orthovanadate (Na3VO4) demonstrated a time and dose-dependent inhibition of autocrine growth of the human carcinoma cell lines A549 (lung), HTB44 (kidney) and DU145 (prostate), as compared to appropriate controls (without Na3VO4). The investigation was conducted by two methods: staining with N-hexa-methylpararosaniline (crystal violet=CV) or bromide3-(4,5-dimethyltio-azo-2)-2,5-diphenyl-tetrazole (MTT). In 5, 10 and 20 microM of Na3VO4 in serum-free medium, the mean values of these two tests for A549 were approximately 40%, 45% or 65% as compared to the appropriate controls. HTB44 had the greatest opportunity (statistically insignificant) at lower vanadium concentrations (up to 10 microM), whereas at 20 microM growth inhibition of these cells was approximately 50% of the controls. DU145 showed approximately 33%, 65% and 98% growth inhibition for 5, 10 and 20 microM of Na3VO4, respectively Additionally, hypothetical curves obtained by a MANOVA test based on the CV results after 72 h incubation with Na3VO4 in serum-free medium, and an example of a time-dependent effect of Na3VO4 on A549 cells, were also presented. Sodium orthovanadate was also examined for its cytotoxic capabilities, especially its ability to induce tumor cell apoptosis; the results were compared with the effect of paclitaxel. The target cells were dyed by differential staining (HOECHST33258 and propidium iodide) after 3 h and 24 h (DU145) or 3 h and 72 h (A549) of incubation with the vanadium compound. Contrary to the two cancer cell lines (viable, apoptotic or necrotic in experimental conditions), the renal HTB44 cells were insensitive up to 15 microM Na3VO4 concentrations. After 3 h incubation with Na3VO4, both lung (A549) and prostate (DU145) cancer cells showed a slight but significant reduction in the percentage of viable cells, and an increased amount of apoptotic cells. In contrast to the lung cells, DU145 prostate cells after 24 h were more sensitive to paclitaxel than to sodium orthovanadate. In the case of lung cells, the time of incubation was prolonged (to 72 h) to allow for a study of the effect of orthovanadate in greater detail. After 72 h of incubation with Na3VO4 or paclitaxel, A549 showed a similar level of viable cells (25-32% of total cultured cells); however, the percentage of apoptotic cells was higher in the case of A549 cells--ca 36% for both drugs, but the concentration of Na3VO4 was significantly greater than paclitaxel levels.
3.
Sigma receptor ligands protect human retinal cells against oxidative stress.
Bucolo, C, Drago, F, Lin, LR, Reddy, VN
Neuroreport. 2006;(3):287-91
Abstract
This study was undertaken to investigate the role of sigma receptors during the oxidative damage on human retinal pigment epithelial cells, and to assess whether sigma receptor ligands enhance survival and protect DNA of cells challenged by oxidative stress. Pretreatment with PRE-084, a sigma1 receptor agonist, resulted in significant increased viability in a dose-related manner. DNA damage induced by oxidative insult was significantly lower with PRE-084. The effects of PRE-084 were antagonized by pretreatment with sigma1 receptor antagonists (NE-100 and BD1047), but interestingly were synergized by cotreatment with BD1047 that also presented an affinity for the sigma2 receptor. The results suggest that sigma1 receptors play an important role against retinal damage, even though sigma2 receptor involvement cannot be excluded.
4.
Colonic epithelial cell proliferation decreases with increasing levels of serum 25-hydroxy vitamin D.
Holt, PR, Arber, N, Halmos, B, Forde, K, Kissileff, H, McGlynn, KA, Moss, SF, Kurihara, N, Fan, K, Yang, K, et al
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2002;(1):113-9
Abstract
Epidemiological evidence suggests a potential role for vitamin D in colon cancer prevention. Vitamin D, absorbed from the intestine or derived from solar ultraviolet light, is metabolized in the liver to 25-hydroxyvitamin D (25-OH D(3)). Previous studies examining effects of vitamin D upon carcinogenesis have focused upon the active metabolite 1,25-dihydroxyvitamin D [1,25-(OH)(2) D(3)], which interacts with nuclear vitamin D receptors in several organs. Until recently, the metabolism of 25-OH D(3) to 1,25-(OH)(2) D(3) was believed to occur only in the kidney, but more recent studies have shown that 25-OH D(3) conversion to 1,25-(OH)(2) D(3) can occur in other tissues. We examined the association between fasting levels of 25-OH D(3), 1,25-(OH)(2) D(3), and BsmI polymorphism of the vitamin D receptor (VDR) gene with indices of colonic epithelial cell proliferation and differentiation in a chemoprevention study, after giving vitamin D or calcium and taking rectal biopsies that were incubated with bromodeoxyuridine. Vitamin D receptor polymorphism was determined by genotyping of the 3' BsmI polymorphism in intron eight of the VDR gene. No significant changes in cell proliferation or in differentiation were found in subjects between study start and end. However, fasting serum levels of 25-OH D(3) showed a highly significant decrease with whole crypt labeling index and the size of the proliferative compartment (phi h). There was no correlation between serum levels of 1,25-(OH)(2) D(3) and the proliferative parameters. Calcium supplementation induced a significant effect upon the relationship between serum 25-OH D(3) and rectal epithelial cell labeling index and phi h when studied by covariance analysis without a relationship with 1,25-(OH)(2) D(3) levels. VDR genotype did not influence the effects of serum 25-OH D(3) or serum 1,25-(OH)(2) D(3) levels upon proliferation. These data suggest that there might be a local effect of 25-OH D(3) on colonic epithelial cells through conversion of 25-OH D(3) to 1,25-(OH)(2) D(3). Subsequent studies have demonstrated the presence of 1alpha-hydroxylase mRNA in normal colorectal epithelium and in colorectal cancer. Thus, vitamin D may have an important role in determining the effects of calcium on colorectal epithelial proliferation and may explain some of the discrepancies found previously in studies that examine the direct role of calcium on the colorectal epithelium.